The normal age-related decline in kidney function has been proposed to be due to, at least in part, increased oxidative stress, which can induce mitochondrial leak respiration via activation of uncoupling proteins. Indeed, two-year old mice deficient of uncoupling protein-2 presented with improved mitochondria efficiency and reduced urinary protein excretion.

Summarizing, the data presented in this thesis provide clear support for potent influence of the renin-angiotensin-aldosterone system, HIF activation and mitochondria function on intrarenal oxygen availability. Maintaining kidney oxygen homeostasis may be a unifying strategy to protect kidney function.